The research described in this application is designed to characterize the regulatory properties of the pyruvate dehydrogenase multienzyme complex in the rat brain. Metabolic flux through the pyruvate dehydrogenase reaction, the activation state of the enzyme complex and the level of phosphorylation of the enzyme will be determined in mitochondrial and synaptosomal preparations derived from several individual regions of the brain taken from adult rats and from rats during their early developmental stages. The regulation of pyruvate dehydrogenase or pyruvate metabolism in general will be investigated in perfused brains derived from adult rats and developing rats. The effects of alterations in the hormal and/or the nutritional state of the animal on the regulatory parameters for the pyruvate dehydrogenase complex will be investigated in this metabolic preparation. The long range goal of this research project is to document the crucial relationship between the ability ofthe brain to regulate its important energy generating pathways and the maintenance of neuro-logical competence in this tissue.